Metabolism of harmaline in rats

The distribution and metabolic fate of [ 3H]harmaline-HCl were studied in rats. Thirty min after subcutaneous injection, high radioactivity was found in the small intestine, liver, adrenals, kidneys and lungs. A rapid turnover and elimination was evident after the first hour, as most of the tissues, except the liver, kidneys and intestines, had decreased nearly 50 per cent in levels of radioactivity. About 40 per cent of the harmaline was bound to human serum or rat serum proteins in vitro. The blood levels, however, were low at all times in vivo. The peak concentration in the brain occurred at 1 hr postinjection. The major route of excretion of harmaline and its metabolites was through the kidneys; a total of 62 per cent of the injected dose was excreted in the urine during 96 hr as compared to only 11·5 per cent in the feces over the same period. The major fate of harmaline in rats was demethylation to form harmalol, which was predominantly excreted as the glucuronide conjugate. Six to 10 per cent of the radioactivity was identified as the sulfate conjugate of harmol, which was formed by the dehydrogenation of harmalol. During the first 8 hr, unchanged harmaline in the urine amounted to about 25 per cent; however, this decreased to only 7 per cent during the 8–24 hr period.